PT  - JOURNAL ARTICLE
AU  - Androniqi Qifti
AU  - Lela Jackson
AU  - Ashima Singla
AU  - Osama Garwain
AU  - Suzanne Scarlata
TI  - Stimulation of Gαq Promotes Stress Granule Formation
AID  - 10.1101/521369
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 521369
4099  - http://biorxiv.org/content/early/2019/05/18/521369.short
4100  - http://biorxiv.org/content/early/2019/05/18/521369.full
AB  - During adverse conditions, mammalian cells regulate protein production by sequestering the translation machinery in membraneless organelles (i.e. stress granules) whose formation is carefully regulated. Here, we show a direct connection between G protein signaling and stress granule formation through phospholipase Cβ1 (PLCβ1). In cells, PLCβ1, the most prominent isoform of PLCβ in neuronal cells, localizes to both the cytoplasm and plasma membrane. Here, we show that a major population of cytosolic PLCβ1 binds to stress granule proteins, such as PABPC1, eIF5A and Ago2. PLCβ1 is activated by Gαq in response to hormones and neurotransmitters and we find that activation of Gαq shifts the cytosolic population of PLCβ1 to the plasma membrane, releasing stress granule proteins. This release is accompanied by the formation of intracellular particles containing Ago2 aggregates, an increase in the size and number of particles containing PABPC1 and Ago2, and a shift of cytosolic RNAs to larger sizes consistent with cessation of transcription. These particles are seen when the cytosolic level of PLCβ1 is lowered by siRNA, osmotic stress or Gαq stimulation by carbachol. These stresses, in addition to cold, heat, oxidative and arsenite stress produces particles that appear to have different molecular compositions. Our results fit a simple thermodynamic model in which cytosolic PLCβ1 solubilizes stress granule proteins and its movement to Gαq upon stimulation releases these particles to allow the formation of stress granules. Taken together, our studies show a link between Gαq-coupled signals and transcription through stress granule formation.